Protective effect against toxoplasmosis in mice induced by DNA immunization with gene encoding Toxoplasma gondii ROP18

Vaccine. 2011 Sep 2;29(38):6614-9. doi: 10.1016/j.vaccine.2011.06.110. Epub 2011 Jul 14.

Abstract

Toxoplasma gondii is an obligate intracellular protozoan parasite infecting mammals and birds including humans. Rhoptry protein 18 has been implicated as an important virulence factor. In this study, we constructed a DNA vaccine expressing rhoptry protein 18 (ROP18) of T. gondii, and evaluated the immune response and protective immunity in Kunming mice. The gene sequence encoding ROP18 was inserted into the eukaryotic expression vector pVAX I. Intramuscular immunization of mice with pVAX-ROP18 elicited specific humoral responses and stimulated lymphoproliferation (P<0.05). The cellular immune response was associated with the production of IFN-γ, indicating that a Th1 type response was elicited, which was confirmed by the production of large amounts of IgG2a (P<0.05). By the expression of the CD69, an activation marker of CD4+ and CD8+ T cells, we found that pVAX-ROP18 enhanced the activation of CD4+ and CD8+ T cells in lymphoid in mice. After lethal challenge, the mice immunized with the pVAX-ROP18 showed a significantly increased survival time (27.9±15.1 days) compared with control mice which died within 7 days of challenge (P<0.05). Our results show for the first time, that a ROP18 vaccine construct can enhance the T. gondii-specific CTL. Th1 responses and increased survival suggested that ROP18 is a promising vaccine candidate against infection with T. gondii.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / blood
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Proliferation
  • Disease Models, Animal
  • Female
  • Immunoglobulin G / blood
  • Injections, Intramuscular
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / immunology
  • Mice
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / immunology*
  • Protozoan Proteins
  • Protozoan Vaccines / administration & dosage
  • Protozoan Vaccines / genetics
  • Protozoan Vaccines / immunology*
  • Rodent Diseases / prevention & control
  • Survival Analysis
  • Toxoplasmosis, Animal / prevention & control*
  • Vaccination / methods*
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*

Substances

  • Antibodies, Protozoan
  • Immunoglobulin G
  • Protozoan Proteins
  • Protozoan Vaccines
  • Vaccines, DNA
  • Interferon-gamma
  • Protein Serine-Threonine Kinases
  • ROP18 protein, Toxoplasma gondii